A Promising Copper(II) Complex as Antifungal and Antibiofilm Drug against Yeast Infection.

The high mortality rate of candidemia and the limited option for the treatment of Candida spp. infection have been driving the search for new molecules with antifungal property. In this context, coordination complexes of metal ions and ligands appear to be important. Therefore, this study aimed to synthesize two new copper(II) complexes with 2-thiouracil and 6-methyl-2-thiouracil ligands and to evaluate their mutagenic potential and antifungal activity against Candida. The complexes were synthesized and characterized by infrared vibrational spectroscopy, CHN elemental analysis, UV-Vis experiments and ESI-HRMS spectrometry studies. The antifungal activity was evaluated by broth microdilution against 21 clinical isolates of Candida species. The mutagenic potential was evaluated by the Ames test. The complexes were Cu(Bipy)Cl2(thiouracil) (Complex 1) and Cu(Bipy)Cl2(6-methylthiouracil) (Complex 2). Complex 1 showed fungicidal and fungistatic activities against all isolates. Furthermore, the Minimum Inhibitory Concentration (MIC) from 31 to 125 µg/mL and inhibition percentage of 9.9% against the biofilms of C. krusei and C. glabrata were demonstrated. At the concentrations tested, complex 1 exhibited no mutagenic potential. Complex 2 and the free ligands exhibited no antifungal activity at the concentrations evaluated. Since complex 1 presented antifungal activity against all the tested isolates and no mutagenic potential, it could be proposed as a potential new drug for anti-Candida therapy.

Yeasts isolated from nosocomial urinary infections: antifungal susceptibility and biofilm production / Levaduras aisladas de pacientes con infecciones urinarias nosocomiales: sensibilidad antifúngica y producción de biofilm

Background. Urinary Candida infections in the hospital environment are frequent and need to be better understood. Aims. To compare the results of antifungal susceptibility profiles of yeasts isolated from patients with urinary infections obtained by broth microdilution method (BM) and by disk diffusion (DD), and also evaluate the capacity of these yeasts to form biofilms. Methods. Only yeasts obtained from pure urine cultures with counts higher than 105 colony-forming units per milliliter, without bacteria development, of symptomatic patients were included. The isolates were identified by classical methods and the antifungal susceptibility tests were performed with the following drugs: amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole and caspofungin. The biofilm studies were carried out in polystyrene microtitration plates. Results. Ninety-five yeasts isolates were analyzed, including 40 Candida albicans, 31 Candida glabrata, 24 Candida tropicalis. In general, the majority of the isolates were susceptible to the tested drugs but some resistance was observed, especially against fluconazole. Great variability in the antifungal susceptibility results was observed with the different tested drugs and a few discrepancies were observed between both methods. We suggest that in case of DD resistance this result should be confirmed by BM, the standard method. C. tropicalis isolates showed high biofilm production (91.7%) compared to C. albicans (82.5%) and C. glabrata (61.3%), with statistical significance (p = 0.0129). Conclusions. Candiduria in critical patients requires major attention and a better control. The different susceptibility results obtained in this study showed the need to identify yeasts up to the species level, especially in patients with urinary tract infection. The development of techniques of antifungal susceptibility tests can help the clinicians in the empiric treatment of candiduria (AU)

Antecedentes. Las infecciones urinarias producidas por especies del género Candida en el ámbito hospitalario son frecuentes, por lo que se requieren mayores conocimientos. Objetivos. Examinar los resultados de los perfiles de sensibilidad de las levaduras aisladas de pacientes con infección urinaria a los fármacos antimicóticos, comparar los resultados obtenidos con las técnicas de microdilución en caldo y difusión en agar con disco, y valorar la capacidad de estas levaduras para producir biofilm. Métodos. Solo se incluyeron en el estudio las levaduras obtenidas a partir de urocultivos puros de pacientes sintomáticos con recuentos superiores a 105 unidades formadoras de colonias, sin el desarrollo de bacterias. Las levaduras se identificaron con técnicas clásicas y se realizaron pruebas de sensibilidad frente a los antimicóticos siguientes: anfotericina B, ketoconazol, fluconazol, itraconazol, voriconazol y caspofungina. Los exámenes de producción de biofilm se efectuaron en placas de microtitulación de poliestireno. Resultados. Se analizaron 95 aislamientos de levaduras que incluían 40 Candida albicans, 31 Candida glabrata y 24 Candida tropicalis. En general, la mayoría de los aislamientos eran sensibles a los fármacos examinados, aunque se observaron algunas resistencias, en especial al fluconazol. Se observó una variabilidad considerable en los resultados de la sensibilidad a los diferentes antimicóticos examinados, detectándose algunas discrepancias entre ambos métodos de examen. Sugerimos que los casos valorados como resistentes por difusión con disco se confirmen mediante microdilución en caldo, que es el método de referencia. Los aislamientos de C. tropicalis mostraron una elevada producción de biofilm (91,7%) en comparación con C. albicans (82,5%) y C. glabrata (61,3%), siendo la diferencia estadísticamente significativa (p = 0,0129). Conclusiones. Es preciso prestar mayor atención a la candiduria detectada en pacientes en estado crítico, al igual que un mejor control. Los diferentes resultados de sensibilidad a los antimicóticos obtenidos en el presente estudio demuestran la necesidad de identificar las especies de las levaduras aisladas de pacientes con infecciones del tracto urinario. El progreso de las técnicas de sensibilidad a los antimicóticos puede ayudar a los médicos en el tratamiento empírico de la candiduria (AU)